Effects of chronic antidepressant drug administration and electroconvulsive shock on activity of dopaminergic neurons in the ventral tegmentum

Abstract

Increasing attention is now focused on reduced dopaminergic neurotransmission in the forebrain as participating in depression. The present paper assessed whether effective antidepressant (AD) treatments might counteract, or compensate for, such a change by altering the neuronal activity of dopaminergic neurons in the ventral tegmental area (VTA-DA neurons), the cell bodies of the mesocorticolimbic dopaminergic system. Eight AD drugs or vehicle were administered to rats for 14 d via subcutaneously implanted minipumps, at which time single-unit electrophysiological activity of VTA-DA neurons was recorded under anaesthesia. Further, animals received a series of five electroconvulsive shocks (ECS) or control procedures, after which VTA-DA activity was measured either 3 d or 5 d after the last ECS. Results showed that the chronic administration of all AD drugs tested except for the monoamine oxidase inhibitor increased the spontaneous firing rate of VTA-DA neurons, while effects on 'burst' firing activity were found to be considerably less notable or consistent. ECS increased both spontaneous firing rate and burst firing of VTA-DA neurons. It is suggested that the effects observed are consistent with reports of increased dopamine release in regions to which VTA neurons project after effective AD treatment. However, it is further suggested that changes in VTA-DA neuronal activity in response to AD treatment should be most appropriately assessed under conditions associated with depression, such as stressful conditions.

Figure 1

Electrophysiological measures of neuronal activity of dopaminergic neurons in the ventral tegmental area (VTA-DA neurons) after chronic administration (for 14 days) via subcutaneously-implanted minipump of vehicle or different antidepressant drugs. For key to abbreviations for the various groups, see “Drugs” in METHODS. Doses of drugs administered are shown below bars. Means and standard errors are shown. The number of animals in each group was n=5 except for VEH n=10 (n=5 SSRI vehicle and n=5 distilled water vehicle), VEN 40 n=6, and PHEN 5 n=6; the number of cells recorded in each animal was 10 except for one animal in each of the following groups: VEH (distilled water vehicle)-7 cells, PAR 1.25–6 cells, and PHEN-6 cells. At top (A) is shown the spontaneous firing rate of VTA-DA neurons, and at bottom (B) is shown the percent of spikes that occurred within bursts. The data for each measure were analyzed by a one–way analysis of variance and a significant effect of drug condition was found for the data shown in (A) F (14,842) = 9.86, p < .001, and (B) F (14,842) = 5.56, p < .001, followed by comparisons of individual drug groups with the vehicle condition done by Dunnett’s test. * = significantly different (at least p < .05) from vehicle.

Figure 2

Electrophysiological measures of neuronal activity of dopaminergic neurons in the ventral tegmental area (VTA-DA neurons) after a series of five electroconvulsive shocks (ECS) or equivalent procedures with no shock being given (Control). Measurement was made either three days (3 Day) or five days (5 Day) after the last shock or control procedure of the series; data are also shown for both recording times combined (3 & 5 Day). Means and standard errors are shown. The number of animals in each group was n=5 for each of the two ECS groups and n=3 for each of the two Control groups; the number of cells recorded in each animal was 10. At top (A) is shown the spontaneous firing rate of VTA-DA neurons, and at bottom (B) is shown the percent of spikes that occurred within bursts. Statistics: significance of the difference between the ECS and control condition at each time point and also both time points combined; (far right) for each measure was determined by a t-test. * = significantly different (at least p. <.05 one tailed) from the Control condition.